Analytical and Formulation Development

Analytical Development and Characterization of ADCs and other Bioconjugates

At WuXi XDC, we leverage in-house expertise and state-of-the-art analytical equipment to characterize the distinct intermediates (e.g., protein/mAb, payload and linker) and the bioconjugate or antibody drug conjugate (ADC) therapeutic candidates at various stages of development. Methods utilized to assess and characterize these complex bioconjugated molecules include UV/VIS, HPLC, cIEF, LC-MS amongst others as is analytical assessment of drug-to-antibody ratio, free-drug content, ADC affinity, protein concentration, aggregation, PI, peptide mapping and potency tests.

Methods utilized to assess and characterize these complex bioconjugated molecules include (but are not limited too):

HPLC

- Drug-to-Antibody Ratio
- Conjugation Efficiency
- Aggregation
- Free Drug Residue

MALS

- Aggregation
- Nanoparticle Characterization

LC-MS

- Drug-to-Antibody Ratio
- Conjugation Efficiency
- Free Drug Residue
- Peptide Mapping

Plate Reader

- Ligand Binding/Affinity
- In vitro Potency Test

Capillary Electrophoresis (CE) and Capillary Isoelectric Focusing (CIEF)

- Non-Reduced & Reduced (CE-SDS)
- Determination of pI (cIEF or iCIEF)

UV/Vis (NanoDrop and SoloVPE^®)

- Protein Concentration
- Drug-to-Antibody Ratio

Additional Bioconjugate Characterization Capabilities:

Capillary Electrophoresis (Charge Heterogeneity and Product-related Impurities)
Native MS (Intact Molecular Weight Determination under Native Conditions)
Peptide Mapping (Conjugated Sites and Occupancy)
Accurate Kd Determination

Formulation and Drug Product Development

We offer extensive end-to-end services for formulation/process development for a wide variety of bioconjugates. Our team assists from early-stage molecular assessments to development of First-in-Human (FIH) formulations to enable clinical trial starts. Additionally, we further provide commercial formulations lock and process/device development in preparation for product launches.

We are experts in developing liquid, frozen or lyophilized dosage forms filled into vials as well as special dosage forms for products containing nanoparticles and other advanced molecular complexes.

Services Overview
Instrument List

Our services include, but are not limited to:

Forced degradation studies to identify product degradation pathways
High-throughput screening (HTS) for formulation development utilizing biophysical methods
Design of Experiment (DOE) to identify the optimal formulations
Container and closure selection and integrity testing
End-to-end fill process development from drug substance thawing through mixing, filtration, filling, stoppering and capping to final visual inspection
Processes development for isolator-based filling systems
Pilot scale (non-GMP) fill finish and lyophilization services for pre-clinical toxicology studies, non-GMP stability studies and scale-down process development
Lyophilization cycle development and optimization
Fill finish and lyophilization process scale-up and/or technology transfer, from development to clinical phase or commercial manufacturing
In-use compatibility and stability studies to support clinical administration or toxicology studies
Stability studies to support formulation and process development under long-term, accelerated or stressed conditions

A partial list of key, cutting-edge equipment used in formulation development includes:

mDSC
DLS
Rheometer
Freeze-drying microscope
DSC
KF moisture analyzer
FTIR microscope
Automated screening station
High throughput buffer exchange
CG-MALS
Filling line
Lyophilizer
Freeze-thaw System
MFI
HIAC
Headspace analyzer
Silicone oil distribution analyzer